A Multi-center, Double-blind, Placebo-controlled Phase 4 Study in Patients With Pulmonary Arterial Hypertension to Assess the Effect of Selexipag on Daily Life Physical Activity and Patient's Self-reported Symptoms and Their Impacts
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 108
- 试验地点
- 39
- 主要终点
- Change From Baseline to Week 24 in Total Sleep Time (TST)
研究概览
简要总结
The primary objective of this study is to evaluate the effect of selexipag on the physical activity of patients with pulmonary arterial hypertension (PAH) in their daily life, by using a wearable wrist device (actigraph). The actigraph will collect data on daily life physical activity in the patient's real environment. In addition, the PAH symptoms and their impacts will be assessed by using an electronic patient reported outcome measure in the patient's real environment. Patients will be assigned randomly to either selexipag or placebo.
详细描述
This study is designed as exploratory with the purpose to generate hypotheses on new endpoints
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female between 18 and 75 years old inclusive.
- •Women of childbearing potential must have a negative serum pregnancy test at planned visits and use an acceptable method of birth control from screening up to 30 days after study treatment discontinuation.
- •Symptomatic pulmonary arterial hypertension (PAH) belonging to one of the following subgroups only:
- •Idiopathic
- •Heritable
- •Drug or toxin induced
- •Associated with one of the following: connective tissue disease; HIV infection; corrected simple congenital heart disease.
- •With the following hemodynamic characteristics assessed by right heart catheterization (RHC) prior to randomization:
- •Mean pulmonary artery pressure (mPAP) ≥ 25 mmHg
- •Pulmonary vascular resistance (PVR) ≥ 240 dyn•sec/cm5 (or 3 Wood Units)
- •Pulmonary artery wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) ≤ 15 mmHg.
- •Treatment with an endothelin receptor antagonist (ERA) for at least 90 days and on a stable dose for 30 days prior to randomization.
- •If an ERA is given in combination with a phosphodiesterase-5 (PDE-5) inhibitor or soluble guanylate cyclase (sGC) stimulator, these treatments must be ongoing for at least 90 days and on a stable dose for 30 days prior to randomization.
- •WHO functional class (FC) II or III at randomization
- •6-minute walk distance (6MWD) ≥ 100 m at screening.
- •Ability to walk without a walking aid.
- •Valid baseline data for daily life physical activity (DLPA) and PAH-SYMPACT®.
排除标准
- •Patients on a PAH-specific monotherapy targeting the nitric oxide pathway (i.e. PDE-5 inhibitor or sGC stimulator).
- •Patients treated with prostacyclin, prostacyclin analog or selexipag within 3 months prior to screening.
- •Any hospitalization during the last 30 days prior to screening.
- •Severe coronary heart disease or unstable angina.
- •Documented severe hepatic impairment or severe renal insufficiency at screening.
- •Participation in a cardio-pulmonary rehabilitation program based on exercise training within 8 weeks prior to screening
- •Any factor or condition likely to affect full participation in the study or compliance with the protocol (such as adherence to protocol mandated procedures), as judged by the investigator.
研究组 & 干预措施
Selexipag
Selexipag is up-titrated from Day 1 to Week 12 to the individualized highest tolerated dose (HTD), which can range from 200 mcg b.i.d. to 1600 mcg b.i.d., in 200 mcg steps starting with 200 mcg b.i.d. Then, the dose is increased in increments of 200 mcg b.i.d., usually at weekly intervals, depending on the dose tolerability. Up-titration is followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.
干预措施: Selexipag (Drug)
Placebo
Regimen and titration scheme similar to those in the selexipag group
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline to Week 24 in Total Sleep Time (TST)
时间窗: Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)
TST (in minutes) was assessed by actigraphy.
Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Counts
时间窗: Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)
Change from baseline to Week 24 of the DLPA activity parameters for volume of non-sedentary activity (Koster '16)were reported. These variables were assessed by actigraphy and were expressed in counts. Koster 2016 defined the threshold between sedentary and NSA based on wrist-worn accelerometers on non-dominant hand, respectively. Positive change from baseline means improvement.
Change From Baseline to Week 24 in Wake After Sleep Onset (WASO)
时间窗: Baseline and Week 24 (data collection was done during 14-Days each for Baseline and for Week 24)
WASO (in minutes) was assessed by actigraphy.
Change From Baseline to Week 24 in Actigraphy Assessed Daily Life Physical Activity (DLPA) for Variables Expressed in Minutes
时间窗: Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)
Change from baseline to Week 24 of the DLPA activity parameters for daily time spent in non-sedentary activity (NSA) (as defined by Freedson '98 and Koster '16) and daily time spent in moderate-to-vigorous physical activity (MVPA) as defined by Freedson '98 were reported. These variables were assessed by actigraphy and were expressed in minutes. Freedson 1998 established ranges of activity counts obtained from a hip worn accelerometer corresponding to commonly employed MET categories. Based on this work, threshold between sedentary and NSA was defined. This threshold is often referred to as Freedson's 1998 publication. Koster 2016 defined the threshold between sedentary and NSA based on wrist-worn accelerometers on non-dominant hand, respectively. Positive change from baseline means improvement.
Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Counts Per Minute (Counts/Minute)
时间窗: Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)
Change from baseline to Week 24 of the DLPA activity parameter for total daily activities and NSA (Koster '16) were reported. These variables were assessed by actigraphy and were expressed in counts/minutes. Koster 2016 defined the threshold between sedentary and NSA based on wrist-worn accelerometers on non-dominant hand, respectively. Positive change from baseline means improvement.
Change From Baseline to Week 24 in Actigraphy DLPA for Variable Expressed in Step Counts
时间窗: Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)
Change from baseline to Week 24 of the DLPA activity parameters for number of steps during awake time were reported. These variables were assessed by actigraphy and were expressed in step counts. Positive change from baseline means improvement.
Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Step Counts/Minute
时间窗: Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)
Change from baseline to Week 24 of the DLPA activity parameters for number of steps during awake time were reported. These variables were assessed by actigraphy and were expressed in step counts/minute. Positive change from baseline means improvement.
Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Percentage (%)
时间窗: Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)
Change from baseline to Week 24 of the DLPA activity parameters for daily time spent in non-sedentary activity (NSA) (Freedson '98), daily time spent in moderate-to-vigorous physical activity (MVPA) (Freedson '98) and dailytime spent in NSA (Koster '16) were reported. These variables were assessed by actigraphy and were expressed in percentage (%). Freedson 1998 established ranges of activity counts obtained from a hip worn accelerometer corresponding to commonly employed MET categories. Based on this work, threshold between sedentary and NSA was defined. This threshold is often referred to as Freedson's 1998 publication. Koster 2016 defined the threshold between sedentary and NSA based on wrist-worn accelerometers on non-dominant hand, respectively. Positive change from baseline means improvement.
Change From Baseline to Week 24 in Number of Awakenings
时间窗: Baseline and Week 24 (data collection was done during 14-Days each for Baseline and for Week 24)
Number of awakenings was assessed by actigraphy.
Change From Baseline to Week 24 in Sleep Efficiency (SE)
时间窗: Baseline and Week 24 (data collection was done during 14-Days each for Baseline and for Week 24)
SE (in percentage) was assessed by actigraphy. Sleep efficiency was defined as the TST divided by the time in bed (minutes) multiplied by 100. TST was the duration in minutes including REM sleep plus NREM sleep during the time spent in bed.
次要结局
- Change From Baseline to Week 24 in 6-Minute Walk Distance (6MWD)(Baseline and Week 24)
- Change From Baseline to Week 24 in N-Terminal Pro B-type Natriuretic Peptide (NT-proBNP)(Baseline and Week 24)
- Change From Baseline to Week 24 in Borg Dyspnea Score(Baseline and Week 24)
- Number of Participants With Change From Baseline to Week 24 in World Health Organization Functional Class (WHO FC)(Baseline and Week 24)
- Change From Baseline to Week 24 in Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Score(Baseline and Week 24)